The long-term objective of this program is to understand the mechanism(s) of neoplastic transformation through use of mammalial cells in culture. Because of the relevance of epithelial cells to human carcinogenesis, epithelial cell proliferation and functional expression are of interest. Defining environmental conditions for sustained expression of differentiated function in culture is pertinent because of possible relationship between transformation of epithelial cells and changes in differentiated function. Studies include: (a) Impact of environmental conditions on differentiated function in two model systems, maturation or terminal differentiation of mouse epidermal keratinocytes and formation of hemicysts, a manifestation of transepithelial ion and fluid movement, in secreting epithelium. Investigating conditions for rapid proliferation of basal cells and conditions that trigger terminal differentiation, we found that normal human and C3H epidermal keratinocytes in mass culture proliferate more rapidly to higher cell density if calcium ion concentration is increased above levels for optimal clonal growth. Further, limiting protein synthesis by cycloheximide treatment enhances terminal differentiation in mouse keratinocytes, and even at low calcium ion concentration normal and neoplastic mouse keratinocytes maintain a capacity for maturation. In monkey kidney epithelium dissolved oxygen concentration modules hemicyst formation. Also, oxygen consumption by epithelial cells is significantly greater than that of fibroblasts, a property that lowers the risk of oxidative injury to epithelium in culture. (b) Association of focal adhesion sites to cell shape change characteristic of neoplastic transformation of mouse and human cells in culture. Photomicrographic data are being quantified by computer-assisted morphometric analysis. (c) Analysis of photosensitivity of xeroderma pigmentosum, Group A, cells (XP-A) to low intensity fluorescent light. Exposure of XP-A cells to low intensity fluorescent light (wave lengths Greater than 300 nm) caused a greater degree of cell killing and/or cytostasis than observed in normal human fibroblasts.